Study suggests gut immune cells cut MS inflammation

January 08, 2019

Researchers at the University of Toronto and UC San Francisco have discovered that the intestine is the source of immune cells that reduce brain inflammation in people with multiple sclerosis. They found increasing the number of these cells blocks inflammation entirely in a preclinical model of the disease.

The cells in question are plasma cells — white blood cells that originate as B cells in the bone marrow, but change their behavior when triggered by microbes in the gut. The researchers found, while studying mice and samples from human MS patients, that plasma cells that reside in the gut and produce Immunoglobulin A antibodies appear to migrate to the central nervous system. The plasma cells also produce an anti-inflammatory effect during MS flare-ups.

Specifically, researchers found evidence in patients with active MS neuroinflammation that IgA was decreased in fecal samples. This suggests that the inflammation-suppressing cells had been recruited to help fight the patients’ disease. The researchers said showing that IgA-producing B cells can travel from the gut to the brain could be the first step towards producing novel treatments to modulate or stop MS and related neurological disorders.

One promising aspect of the new research is that increasing the number of IgA plasma cells that migrate from the gut to the brain eradicated neuroinflammation in mice. A therapeutic approach might aim to expand the number of these cells in the gut, enabling a plentiful supply that could move to the brain and dampen inflammation.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, a key next step for the researchers is to figure out what microbes in the gut promote the generation of immunosuppressive IgA plasma cells. If researchers can understand what these cells are reacting to, they can potentially treat MS by modulating the gut commensals. That might be easier than getting drugs into the brain, which is a strategy that hasn’t always worked in MS.